Impact of Cyclin-dependent Kinase Inhibitor 1A Genotypes on Prostate Cancer Susceptibility Prediction

Prostate cancer is a multifactorial disease influenced by both genetic and environmental factors. Previous studies have identified a correlation between p21 expression and the clinical severity of prostate cancer. However, the contribution of cyclin-dependent kinase inhibitor 1A (CDKN1A), which encodes p21, to prostate cancer susceptibility remains unclear. This study aimed to evaluate the association between CDKN1A polymorphisms rs1801270 and rs1059234 and the risk of prostate cancer in a Taiwanese population.

A total of 218 patients with prostate cancer and 436 cancer-free controls were genotyped for CDKN1A rs1801270 and rs1059234 using the PCR-RFLP method. Genotypic distributions were analyzed for associations with prostate cancer risk overall and stratified by age and smoking status.

No significant association was observed between either CDKN1A rs1801270 or rs1059234 genotypes and overall prostate cancer risk (both p>0.05). However, stratified analysis showed that individuals aged <55 years carrying the rs1801270 variant genotypes (AC and AA) had a significantly increased risk of early-onset prostate cancer [odds ratio (OR)=2.16 and 2.51, 95% confidence interval (CI)=1.25-3.71 and 1.37-4.61, p=0.0069 and 0.0041, respectively]. Additionally, among non-smokers, carriers of the rs1059234 variant genotypes (CT and TT) exhibited a significantly reduced prostate cancer risk (OR=0.27 and 0.36, 95%CI=0.11-0.64 and 0.14-0.98, p=0.0042 and 0.0739, respectively), indicating a potential gene-environment interaction.

While CDKN1A rs1801270 and rs1059234 may not serve as general predictive markers for prostate cancer susceptibility, they appear to modulate prostate cancer risk under specific age and smoking contexts. These findings merit further validation in larger and ethnically diverse populations and may contribute to more refined risk stratification and personalized prevention strategies.